ABSTRACT:The development and evolution of the inner ear sensory patches and their innervation is reviewed. Recent molecular developmental data suggest that development of these sensory patches is a developmental recapitulation of the evolutionary history. These data suggest that the ear generates multiple, functionally diverse sensory epithelia by dividing a single sensory primordium. Those epithelia will establish distinct identities through the overlapping expression of genes of which only a few are currently known. One of these distinctions is the unique pattern of hair cell polarity. A hypothesis is presented on how the hair cell polarity may relate to the progressive segregation of the six sensory epithelia. Besides being markers for sensory epithelia development, neurotrophins are also expressed in delaminating cells that migrate toward the developing vestibular and cochlear ganglia. These delaminating cells originate from multiple sites at or near the developing sensory epithelia and some also express neuronal markers such as NeuroD. The differential origin of precursors raises the possibility that some sensory neurons acquire positional information before they delaminate the ear. Such an identity of these delaminating sensory neurons may be used both to navigate their dendrites to the area they delaminated from, as well as to help them navigate to their central target. The navigational properties of sensory neurons as well as the acquisition of discrete sensory patch phenotypes implies a much more sophisticated subdivision of the developing otocyst than the few available gene expression studies suggest.

ErbB2 protein is essential for the development of Schwann cells and for the normal fiber growth and myelin formation of peripheral nerves. We have investigated the fate of the otocyst-derived inner ear sensory neurons in the absence of ErbB2 using ErbB2 null mutants. Afferent innervation of the ear sensory epithelia shows numerous fibers overshooting the organ of Corti, followed by a reduction of those fibers in near term embryos. This suggests that mature Schwann cells do not play a role in targeting or maintaining the inner ear innervation. Comparable to the overshooting of nerve fibers, sensory neurons migrate beyond their normal locations into unusual positions in the modiolus. They may miss a stop signal provided by the Schwann cells that are absent as revealed with detailed histology. Reduction of overshooting afferents may be enhanced by a reduction of the neurotrophin Ntf3 transcript to about 25% of wild type. Ntf3 transcript reductions are comparable to an adult model that uses a dominant negative form of ErbB4 expressed in the supporting cells and Schwann cells of the organ of Corti. ErbB2 null mice retain afferents to inner hair cells possibly because of the prominent expression of the neurotrophin Bdnf in developing hair cells. Despite the normal presence of Bdnf transcript, afferent fibers are disoriented near the organ of Corti. Efferent fibers do not form an intraganglionic spiral bundle in the absence of spiral ganglia and appear reduced and disorganized. This suggests that either ErbB2 mediated alterations in sensory neurons or the absence of Schwann cells affects efferent fiber growth to the organ of Corti.

In contrast to most other sensory systems, hardly anything is known about the neuroanatomical development of central projections of primary vestibular neurons and how their second order target neurons develop. Recent data suggest that afferent projections may develop not unlike other sensory systems, forming first the overall projection by molecular means followed by an as yet unspecified phase of activity mediated refinement. The latter aspect has not been tested critically and most molecules that guide the initial projection are unknown.The molecular and topological origin of the vestibular and cochlear nucleus neurons is also only partially understood. Auditory and vestibular nuclei form from several rhombomeres and a given rhombomere can contribute to two or more auditory or vestibular nuclei. Rhombomere compartments develop as functional subdivisions from a single column that extends from the hindbrain to the spinal cord. Suggestions are provided for the molecular origin of these columns but data on specific mutants testing these proposals are not yet available. Overall, the functional significance of both overlapping and segregated projections are not yet fully experimentally explored in mammals. Such lack of details of the adult organization compromises future developmental analysis.

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